Conflict of Interest

A person may find him- or herself in a situation where two or more competing interests creates the perception or the reality of an increased risk of bias or poor judgment. Such challenging situations come up regularly in both our personal and professional lives. Collectively, we refer to these as conflicts of interest. This term has become synonymous with monetary or personal gain. It encompasses behaviors or actions in which someone (or a member of their immediate family or household) gains personally or financially as the result of that person exploiting his or her position. Conflict of effort on the other hand involves situations where demands from separate entities jeopardize the duties and responsibilities associated with one of more of those entities (e.g., outside consulting activities interfering with duties of one's primary employment). Yet a third type of conflict is called conflict of conscience. Here the conflict is created by having to maintain objectivity in the face of your convictions which go against the grain of something you must act on or evaluate. Such a conflict might emerge during peer review; e.g., being asked to review a manuscript on fetal stem cell research, when you believe that such research is wrong because the origin of such cells is from aborted fetuses. Conflicts encountered in the profession of science are not inherently bad. Indeed, they are to be expected. It's how they are handled that can lead to untoward, inappropriate, or bad outcomes.

Although scientists have a professional, fiduciary, and ethical interest in the responsible conduct of research, these interests may be compromised by personal interest. A common worry is that financial interest in the outcomes of research can result in unethical behavior or criminal misconduct.

Discussions about conflict of interest generally focus on financial interests, but it is equally plausible that interests other than financial could compromise the responsible conduct of research. Examples of non-financial interests that might conflict with the integrity of science include career advancement, publishable results, service to patients or students, fame, power, or family and friendships. Another potential conflict can come in the form of conscience. An individual might suffer a conflict of interest if the mission or expectation of the institution is not compatible with his or her personal values.

Of course, having a personal interest does not necessarily mean acting irresponsibly. Although some might take personal interest as a motivation for misconduct, it is obvious that not all individuals would make this choice.

Conflicts of interest are not merely a hypothetical problem. Financial conflicts are associated with altered outcomes of research. Stelfox et al. (1998) reviewed the literature in 1995 and 1996 for reports on the safety of calcium channel antagonists. They classified reports as being supportive, neutral, or critical of these drugs. They found that 100% of authors of reports supporting calcium channel antagonists had financial relationships with drug companies, while only 43% of authors of reports critical of the drugs had such connections with drug companies. Many different hypotheses might explain this trend, but one lesson is that it would be valuable to know if a published study was supported by industry.

Rules and Regulations

A variety of regulations and guidelines govern the disclosure and management of conflict of interest. Although many of the concerns addressed could be generalized to any form of conflict of interest, the explicit problem in nearly all cases is financial. The most relevant of these are federal regulations, notably those of the Public Health Service (PHS) and National Science Foundation (NSF).

PHS and NSF policies are substantially the same regarding conflicts of interest (PHS, 1995; NSF, 1995). Under PHS policy: '...investigators are required to disclose to an official(s) designated by the institution a listing of Significant Financial Interests ... that would reasonably appear to be affected by the research proposed for funding by the PHS.' The institutional official(s) are responsible to review 'those disclosures and determine whether any of the reported financial interests could directly and significantly affect the design, conduct, or reporting of the research and, if so, the institution must, prior to any expenditure of awarded funds, report the existence of such conflicting interests to the PHS Awarding Component and act to protect PHS-funded research from bias due to the conflict of interest.' Significant Financial Interests are defined to be: '...anything of monetary value, including, but not limited to, salary or other payments for services (e.g., consulting fees or honoraria); equity interests (e.g., stocks, stock options or other ownership interests); and intellectual property rights (e.g., patents, copyrights and royalties from such rights).'

Professional societies and journals are an important source for guidance on the management of conflicts of interest. These are quite variable in their scope and rarely enforced, but two examples are noteworthy. The first is a policy statement from American Society of Gene Therapy (ASGT), and the second is the published requirements for publication in the New England Journal of Medicine. In a statement adopted in April of 2000, the ASGT concluded that 'investigators and team members directly responsible for patient selection, the informed consent process and/or clinical management in a trial must not have equity, stock options, or comparable arrangements in companies supporting the trial.' (Woo, 2000) As early as 1984, the New England Journal of Medicine requested that 'all authors disclose to [the Editor] any associations they had with businesses that could be affected by their work -- including direct employment and consultancy, stock ownership, and patent-licensing arrangements.' (Angell and Kassirer, 1996).

Federal regulations defer, in part, to institutional definitions of conflicts of interest. Not surprisingly, institutional standards vary greatly. Regarding stock ownership, most use the federally defined threshold of $10,000 or 5% of total shares as a definition of significant financial interest that must be declared. However, some institutions have been somewhat stricter. For example, Harvard scientists are prohibited from working for a company in which they have more than $20,000 in stock (Brainard, 2000).

Principles

Perhaps the adverse consequences of conflicts of interest will eventually be mitigated by the structure of science-- objectivity, blinding of experimenters, repetition of studies, peer review, disclosure, and so on. In practice, this strategy does not address the harms to subjects in clinical trials, misinformation entering the literature, and increased cynicism about science.

Conflicts of interest increase the temptation to commit misconduct. Conflicts of interest do not necessarily amount to research misconduct. If the potential gain is large, however, then principles that guide responsible conduct in research may be compromised.

Conflicts of interest increase the risk of unintentional bias. Unintentional bias can be a more serious threat than deliberate misconduct, because even those who are biased would be unaware of the ways in which their actions were effected.

For example: Because research is expensive, the research interests of individual scientists are likely to drift toward those topics, methods, and approaches for which support is available. In the design of experiments, scientists may be unconsciously biased to choose, or stick with, approaches likely to provide 'marketable' findings, rather than those designed to increase basic understanding of mechanisms. In the collection of data, a researcher with significant financial interests may unwittingly introduce bias into enrollment of subjects for a clinical trial, into evaluation of data dependent on subjective judgments, or even into the reading of objective measurements. Finally, unintentional bias could alter choices about data selection, statistical methods, and presentation of results.

Conflicts of interest can lead to harmful misperceptions of scientists and the scientific enterprise.When large sums of money are involved, it may be difficult for the public, legislators, the judicial system, and even colleagues to be convinced that results were not biased for personal gain. Perceived impropriety can result in consequences as damaging as if intentional misconduct had been committed. With increased media, governmental, and public scrutiny, a researcher's reputation, research funding, and employment can depend as much on perceptions of integrity as on integrity itself.

Guidelines

Beyond the existing rules, the following are guidelines generally applicable to the management of conflicts of interest and commitment:

Avoid and minimize conflictsEveryone has different interests, and eventually these will come into conflict. Although it is not possible to avoid all sources of conflict, it is in the best interests of the scientific community and the individual scientist to recognize conflicts of interest and to take steps to nullify or mitigate those conflicts; for instance, sell shares in the company, turn down research support, or abandon a project.

Disclose interestsIf conflicts cannot be avoided, then those conflicts should be disclosed. At minimum, the institution and any other parties with a significant interest should be made aware of the extent and nature of the conflict. This includes the audience at meeting presentations as well as journal editors (before submitting or refereeing manuscripts).

Manage potential for conflictDisclosure is often not enough because of the risks of bias, the temptation for irresponsible conduct, public and regulatory concerns about the possibility of misconduct, and the appearance of impropriety. For every step of the research process, attempts should be made to isolate the conflicted individuals from all decisionmaking functions. For example, steps should be taken to maximize the objectivity of patient selection, data collection, the selection of data for publication, and interpretation of the findings. These functions should be the responsibility of, or should at least be reviewed by, an unconflicted individual or group.

Disclosure usually occurs only for financial interests, and such disclosure is not routine in the biomedical literature (Krimsky et al., 1998). In a survey of 789 scientific papers published by Massachusetts scientists in the leading journals of cell and molecular biology, Krimsky and his colleagues contacted the authors and found that 34% of the articles had at least one Massachusetts author with a significant financial interest. Despite this high rate of financial interests, Krimsky et al. reviewed 62,000 papers and found that only about 0.5% included disclosure statements. Unfortunately, even as financial conflicts and the risks for bias are increasing, a minimal expectation that those conflicts would be disclosed is not being met.

In summary, it is important to understand that both the potential for conflicts of interest and the strategies for dealing with those conflicts are evolving. Considering the potential for misperceptions of a researcher's motives, it is best to assume that good intentions are not enough.

UAF Specific Information

All UAF personnel should be familiar with the following UAF Policy related to Conflicts of Interest and Commitment.

A form for disclosing Significant Financial Conflicts of Interest is available on the OSP website. If you are uncertain about whether or not something qualifies as a conflict of interest contact the Director, Office of Sponsored Programs f or more information. This applies to any member of the research team, their close family members, close friends, or business associates. If you have a conflict of interest you are required to report it on the OSP Routing Form and work with the Director, Office of Sponsored Programs, to develop a plan to manage or mitigate the conflict.

Although PI's are only required to report significant financial conflicts of interest, they are strongly encouraged to report and develop management plans for other types of conflicts as well. The Director, Office of Research Integrity, c an assist PIs in developing an appropriate management plan.